A Skin Test for Alzheimer's Disease

Scientists aim to commercialize a test that detects an inflammatory marker in skin.

A novel test that detects enzymes that are dysfunctional in patients with Alzheimer's disease--and that are found both in the brain and in skin cells--is about to undergo large clinical trials. Researchers at the Blanchette Rockefeller Neurosciences Institute (BRNI), in Morgantown, WV, who developed the diagnostic have also garnered approval from the Food and Drug Administration to test in humans an experimental drug that activates the enzymes--a mechanism that represents a new therapeutic approach to Alzheimer's.

Sick skin: An experimental diagnostic test for Alzheimer’s disease analyzes the activity of an enzyme in skin. Cultured skin cells (green) from a healthy person (top) and a person with Alzheimer’s disease (bottom) are shown here. Credit: Blanchette Rockefeller Neurosciences Institute

In preliminary clinical trials, the skin test could accurately predict which patients had Alzheimer's disease. Last month, BRNI announced a partnership with Inverness Medical Innovations, a medical diagnostics company based in Waltham, MA, that will fund a larger clinical trial of thousands of patients that is necessary to commercialize the diagnostic.

Currently, Alzheimer's disease can only be definitively diagnosed on autopsy. Physicians diagnose the disease in patients with a combination of cognitive tests to assess mental function, a neurological exam, and brain scans to rule out other problems, such as stroke or brain tumors. But it can be difficult to distinguish between Alzheimer's and other forms of dementia, especially at the early stages of the disease.

"We badly need diagnostic tests for people with mild cognitive impairment and other people at risk for Alzheimer's disease, because there may be in the future disease-modifying therapies that could slow onset or progression of the disease," says Sid Gilman, director of the Michigan Alzheimer's Disease Research Center, at the University of Michigan. A method to accurately diagnose patients in the early stage of the disease could also aid in development of these therapies by allowing physicians to test experimental drugs in only those who need it.

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The new test, developed by Daniel Alkon, scientific director of BRNI, targets a group of enzymes called PKCs, which are involved in long-term memory storage. Alkon and others have found that a select set of these enzymes becomes dysfunctional in Alzheimer's disease, both in brain cells and in skin cells. (While Alzheimer's is primarily considered a neurological disease, research over the past decade has revealed signs of the disease outside of the brain.) In addition, activating the enzymes in animal models of the disease alleviates symptoms, preventing memory loss as well as the abnormal aggregations of protein that build up in the brain.

To perform the test, physicians collect a small sample of skin cells, which are then grown in a dish. Researchers add a specific inflammatory molecule called bradykinin, which activates PKCs under normal circumstances; a dysfunctional response suggests Alzheimer's. Preliminary results from a study of 600 patients are promising: the test correctly diagnosed 36 out of 37 patients confirmed on autopsy to have the disease, as well as 5 patients confirmed on autopsy not to have it.